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Cited by 208Asthma and respiratory diseasesNitric Oxide and Endothelin EffectsInflammatory mediators and NSAID effects

A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics

Hansel, Trevor T., Kharitonov, Sergei A., Donnelly, Louise E., Erin, Edward M., Currie, Mark G., Moore, William M., Manning, Pamela T., Recker, David P. +1 more·2003·The FASEB Journal
DOI 10.1096/fj.02-0633fje
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Abstract

The inducible isoenzyme of nitric oxide synthase (iNOS) generates nitric oxide (NO) in inflammatory diseases such as asthma. The prodrug L-N6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51) is rapidly converted in vivo to the active metabolite L-N6-(1-iminoethyl)lysine (L-NIL). Initially, we performed in vitro experiments in human primary airway epithelial cells to demonstrate that L-NIL causes inhibition of iNOS. In a randomized double-blind placebo-controlled crossover trial, SC-51 was administered as a single oral dose (20 or 200 mg) in separate cohorts of healthy volunteers (two groups of n=12) and mild asthmatic patients (two groups of n=12). SC-51 (200 mg) reduced exhaled breath NO levels to <2 ppb in both healthy volunteers (P<0.001) and mild asthmatics (P<0.001) within 15 min, representing >90% inhibition of baseline levels of NO in asthmatic patients, with the effects lasting at least 72 h. There were no significant effects on blood pressure, pulse rate, or respiratory function (FEV1). This study demonstrates that an inhibitor of iNOS produces marked inhibition of exhaled breath NO in normal and asthmatic subjects without producing the side effects observed following the systemic administration of non-selective NOS inhibitors, and thus provides support for the potential use of iNOS inhibitors to treat a range of inflammatory clinical disorders.

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Crossref · 10.1096/fj.02-0633fje

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  • Deleterious effects of NO on development of COPD might be derived from iNOS-mediated pro-inflammatory signaling, which is consequently reflected by the huge amount of NO in exhaled air of patients with COPD.

    “However, the deleterious effects of NO on the development of COPD might be derived from iNOS-mediated pro-inflammatory signaling [128], which is consequently (not causally) reflected by the huge amount of NO in the exhaled air of patients with COPD [129].”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [128]

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Authors
Hansel, T. T., Kharitonov, S. A., Donnelly, L. E., Erin, E. M., Currie, M. G., Moore, W. M., Manning, P. T., Recker, D. P., & Barnes, P. J.
Affiliations
  • Imperial College London (GB)
  • Sunovion (United States) (US)
  • Pharmacia Corporation Skokie Illinois St. Louis Missouri
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2003-05-08
Volume
17
Issue
10
Pages
1298-1300
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.02-0633fje
OpenAlex
W2132452209
Cited by
208
References
63
Citations by year
2026: 1 · 2025: 1 · 2024: 9 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 10 · 2015: 10 · 2014: 7 · 2013: 8 · 2012: 11
FWCI
12.27
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords
inducible nitric oxide synthase, iNOS inhibitors, exhaled nitric oxide, L-NIL, asthma, airway inflammation, nitric oxide, airway epithelial cells, prodrugs
MeSH terms
Administration, Oral, Adult, Asthma, Breath Tests, Cells, Cultured, Double-Blind Method, Enzyme Inhibitors, Female, Homoarginine, Humans, Lysine, Male, Nitric Oxide, Prodrugs, Cross-Over Studies, Nitric Oxide Synthase, Respiratory Mucosa, Nitric Oxide Synthase Type II

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